DESCRIPTION (adapted from the Abstract): A multidisciplinary, four-year prospective study of the transmission and natural history of human herpes virus is proposed to (1) identify biologic and behavioral risk factors for acquisition of HHV-8/KSHV infection and (2) describe patterns for HHV- 8/KSHV virologic activity, types of host immunologic response, and the relationship of virologic activity and host response to the development of Kaposi's sarcoma (KS). The natural history of HHV-8/KSHV infection will be characterized in patients with and without HIV infection by (a) qualitative and quantitative longitudinal polymerase chain reaction measurement of HHV-8/KSHV in plasma, peripheral blood mononuclear cells, semen and saliva, (b) description of the evolution of anti-latency and anti-lytic phase associated antibodies to HHV-8/KSHV, (c) examination of host cytotoxic T-lymphocyte responses to HHV-8/KSHV at varying stages of infection, and (d) ascertainment of the temporal relationships between virologic activity, host responses, HIV infection, and the development of KS. Two existing cohorts of homosexual men, the San Francisco Men's Health Study and the San Francisco Young Men's Health Study, will be used to identify new seroconversions for antibodies to HHV-8/KSHV latency- associated nuclear antigens (LANA) and to obtain prospective samples of blood, semen, and saliva from men with pre-existing HHV-8/KSHV infection for varying duration, including men who have been seropositive since, at least, 1984. The researchers will follow 300 young men without prior evidence of HHV-8/KSHV infection, or whom 40 are HIV-infected, for the development of anti-LANA seroconversion. Between 35 and 40 incident infections are expected over the four years of follow-up. The natural history of infection will be observed in 200 men with pre-existing HHV- 8/KSHV infection; 100 of these are HIV co-infected.